There is described an isolated 3-dimensional liver spheroid wherein said spheroid has: increased ATP content as compared to a 3-dimensional liver spheroid cultured in Complete William's E medium alone; the same or increased activity of cytochrome P450 1A1 and cytochrome P450 1B1 as compared to a 3-dimensional liver spheroid cultured in Complete William's E medium alone; and increased albumin secretion as compared to a 3-dimensional liver spheroid cultured in William's E medium alone.

Disclosed herein are hepato-biliary-pancreatic organoid (“HBPO” or “HBP organoid”) compositions, and methods of making and using hepato-biliary-pancreatic organoid compositions. The disclosed compositions may have two or more functions selected from hepatic tissue function, biliary tissue function, exocrine pancreatic function, and endocrine pancreatic tissue function. Methods of treating individuals using the hepato-biliary-pancreatic organoid compositions is also disclosed.

The present invention provides a simple and robust human liver cell-based system in which persistent hepatitis C infection, persistent hepatitis B infection or ethanol exposure induces a clinical Prognostic Liver Signature (PLS) high-risk gene signature. The cellular model system for hepatocellular carcinoma (HCC)/cirrhosis development and progression may be used in the screening of compounds useful in the treatment and/or prevention of cirrhosis and/or HCC as well as in the identification biomarkers for the prediction of liver disease (especially cirrhosis) progression and HCC. The present invention also relates to specific compounds that have been identified, using such screening methods, as useful in the treatment and/or the prevention of HCC/cirrhosis.

The invention relates to cell-free compositions obtained by culturing adult-derived human liver stem/progenitor cells (ADHLSC) in cell culture medium and isolating the resulting conditioned medium (ADHLSC-CM) that has advantageous properties, such as anti-fibrotic effects. ADHLSC-CM, compositions based on ADHLSC-CM, and other related and derived products, can be used in cell culture processes or as a medicament, more particularly for the treatment of diseases involving organ injury, organ failure, in organ or cell transplantation or the pathological disruption, inflammation, degeneration, and/or proliferation of cells within a tissue or an organ, in particular within liver.

An objective of the present invention is to provide a liver disease regulatory formulation, which is beneficial to prevent the occurrence and development of a chronic liver disease by remodeling a liver regeneration microenvironment. The liver disease regulatory formulation, comprises a hepatocyte-derived liver progenitor cell or a secretory supernatant of the hepatocyte-derived liver progenitor cell.

The present invention relates to nanoparticles for the targeted delivery of antigen to liver cells, in particular, liver sinusoidal endothelial cells (LSEC) and/or Kupffer cells, and for the in vivo generation of regulatory T cells, notably CD4+CD25+FOXP3+ regulatory T cells (Treg). The invention provides pharmaceutical compositions and methods for the prevention and treatment of autoimmune diseases, allergies or other chronic inflammatory conditions, and for generation of regulatory T cells. The nanoparticles used in the invention comprise a) a micelle comprising an amphiphilic polymer rendering the nanoparticle water-soluble, and b) a peptide comprising at least one T cell epitope associated with the outside of the micelle. The micelle may or may not comprise a solid hydrophobic core.

Provided is a selective method for inducing differentiation from pluripotent stem cells to enterocyte-like cells. Also provided is an excellent enterocyte-like cell expressing drug-metabolizing enzymes and drug transporters. More specifically, provided is an enterocyte-like cell having properties closer to those of primary enterocytes, which are difficult to acquire. The foregoing is achieved by adding an ALK5 inhibitor (SB431542), Wnt3a, and EGF to a culture system of definitive endoderm cells obtained by differentiation induction from pluripotent stem cells and extending a culture time. The foregoing is also achieved by introducing CDX2 gene and/or FOXA2 gene into the pluripotent stem cells or the definitive endoderm cells. The foregoing is also achieved by overlaying a basement membrane matrix on the enterocyte-like cells.

The present disclosure relates to novel multi-organ-chips establishing the differentiation of induced pluripotent stem cell (iPSC)-derived cells into organ equivalents on microfluidic devices and corresponding methods of generating organ equivalents. The present disclosure also relates to novel bioengineered tissue constructs mimicking organ barriers generated with iPSC-derived endothelial cells and/or organoids bioprinted in, and/or seeded on, a hydrogel. The present disclosure further relates to methods of bio-engineering organ constructs comprising co-culturing iPSC-derived organ precursor cells and iPSC-derived fibroblasts and endothelial cells. The present disclosure specifically provides a microfluidic device comprising: (i) iPSC-derived hepatocyte precursor cells; (ii) iPSC-derived intestinal precursor cells; (iii) iPSC-derived renal tubular precursor cells; and (iv) iPSC-derived neuronal precursor cells; wherein the iPSC-derived precursor cells according to (i), (ii), (iii) and (iv) are differentiated from a single donor iPSC reprogrammed from a single type of somatic cell.

Disclosed is a process of manufacturing cell spheroids using a bioink. More particularly, provided is a method of manufacturing a cell spheroid, the method including extruding a first bioink including an alginate; extruding a second bioink including cells into the extruded first bioink; adding a calcium chloride (CaCl2) solution to the alginate included in the first bioink; and dissolving the second bioink, present in the first bioink, in a cell culture medium to form a cell spheroid from the cells.

Disclosed herein are devices and methods for generating orthotopic models of cancer. The devices and methods include providing a microfluidic device having a body, the body including a first microchannel separated from a second microchannel by an at least partially porous membrane, the membrane having a first side facing the first microchannel and a second side facing the second microchannel, seeding the first side of the membrane with healthy cells and cancer cells such that the cancer cells are seeded with a differentiated tissue layer, and culturing the healthy cells and the cancer cells within the microfluidic device by flowing medium through one or more of the first and second microchannels with or without endothelium in the second channel.